TSG-6 expression in human articular chondrocytes: Possible implications in joint inflammation and cartilage degradation

✍ Scribed by Rainer Maier; Hans-Georg Wisniewski; Jan Vilcek; Martin Lotz

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 699 KB
• Volume: 39
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.1780390403

✦ Synopsis

Objective. The hyaluronan-binding protein TSG-6 (tumor necrosis factor-stimulated gene 6) forms a stable complex with the serine protease inhibitor, inter-winhibitor, potentiates the inhibition of plasmin activity, and has antiinflammatory effects in vivo. This study examines the expression of TSG-6 in human articular chondrocytes and cartilage.

Methods. Human articular chondrocytes and cartilage explants were stimulated with cytokines, growth factors, and other agents. TSG-6 expression was analyzed by imaging-assisted Northern and Western blotting .

Results. TSG-6 messenger RNA (mRNA) expression was upregulated by cytokines and growth factors, predominantly interleukin-1 p (IL-1 p), tumor necrosis factor a (TNFcu), platelet-derived growth factor AA (PDGF-AA), and transforming growth factor pl (TGFm). TSG-6 mRNA induction by TGFm was delayed as compared with IGlp. Treatment of the cells with the glucocorticoid dexamethasone neither induced TSG-6 mRNA nor did it affect IL-l&iiduced transcript levels. TSG-6 mRNA induction may involve several signal transduction pathways. The strong transcriptional stimulation by phorbol myristate acetate suggests protein kinase C (PKC)-mediated signaling. In contrast, PKA-and Cadependent signals are only marginally involved as messengers leading to increawd TSG-6 levels after &1/3 and TNFcu treatment. In chondrocyte and cartilage organ cultures, both free TSG-6 (35 kd) and the complex with